The risks of myelodysplastic syndrome (MDS) and acute leukemia are increased in patients previously treated for other malignancies. Therapy-related MDS (t-MDS) occurs after exposure to certain cytotoxic agents or radiation used for cancer treatment. We report a case of t-MDS following curative chemoradiotherapy (CRT) for esophageal and oropharyngeal cancer. An 80-year-old male diagnosed with double cancers of the esophagus and oropharynx underwent definitive CRT and achieved a complete response. Six years later, he became anemic, and bone marrow examination showed 3.4% blast cells with fine chromatin structures and basophilic cytoplasm. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. These findings were consistent with t-MDS. Subsequently, he developed acute myeloid leukemia and died 8 months later. This case indicates that long-term surveillance is needed to closely monitor the risk of t-MDS in patients treated with CRT.